Injection systems

ABSTRACT

Injection systems and devices that can be used in injection systems are disclosed.

CLAIM OF PRIORITY

[0001] This application claims priority under 35 USC §119(e) to U.S.Provisional Patent Application Serial Nos. 60/250,410; 60/250,425;60/250,537; and 60/250,573, all filed on Nov. 30, 2000, and all entitled“Injection Devices”, the entire contents of which are all herebyincorporated by reference.

FIELD OF THE INVENTION

[0002] The invention relates to injection systems and devices that canbe used in injection systems.

BACKGROUND

[0003] Injection devices can be used for injecting fluids, such asdrugs, into a body. Some injection devices, such as needleless injectiondevices, inject fluids by delivering the fluids at a pressure sufficientto create and to sustain in the body an opening through which the fluidsare delivered. A needleless injection device can generate sufficientpressure, for example, by using a compressed gas or a propellant thatgenerates a gas.

SUMMARY

[0004] The invention relates to injection systems and devices that canbe used in injection systems.

[0005] In one aspect, the invention features an injection systemincluding an injector defining a first cavity in fluid communicationwith an orifice configured for needleless injection, and a housinginside the injector and defining a second cavity, the housing differentthan the injector, wherein the injection system is configured totransfer a fluid from the second cavity to the first cavity.

[0006] Embodiments include one or more of the following features. Theinjector is formed of a first material, e.g., a polymer, and the housingis formed of a second material, e.g., a glass, different than the firstmaterial. The system further includes a first movable member between thefirst cavity and the second cavity. The first movable member defines alumen. The system further includes a second movable member between thefirst movable member and the second cavity.

[0007] The first movable member can be configured to engage with thesecond movable member such that the first cavity is in fluidcommunication with the second cavity. The first movable member can beconfigured to be substantially stationary until the first movable memberis moved by a propellant of the injection system. The first movablemember can include a tab configured to separate from the first movablemember at a predetermined force. The tab can engage with the injector.

[0008] The injector and the housing can be substantially coaxial.

[0009] The second cavity can be defined by the housing and two movablemembers. The second cavity can be defined by the housing and a movablemember. The movable member can be formed of two different materials Themovable member can include a rubber.

[0010] The system can further include an injector cap connectable to theinjector, the injector cap configured to move distally to transfer thefluid from the second cavity to the first cavity. The injector cap canbe connectable to the injector by a threaded connection.

[0011] The system can further include a charge cup in the injector. Thesystem can further include a charge in the charge cup. The charge caninclude at least two discrete materials, which can have differentcombustion characteristics.

[0012] In another aspect, the invention features a method includingproviding an injection system having an injector defining a first cavityin fluid communication with an orifice configured for needlelessinjection, and a housing inside the injector and defining a secondcavity, the housing being different than the injector, and reducing thevolume of the second cavity to transfer a fluid from the second cavityto the first cavity.

[0013] Embodiments include one or more of the following features. Themethod further includes flowing the fluid through a movable memberbetween the first and second cavities. The method further includespiercing a member between the first and second cavities. The injectionsystem further includes an injector cap connectable to the injector, andreducing the volume comprises moving the injector cap toward theorifice. Moving the injector cap can include twisting the injector cap.The method can further include moving the fluid through the orificecharge.

[0014] The charge can include at least two discrete materials. The atleast two discrete materials can have different combustioncharacteristics.

[0015] In another aspect, the invention features an injection systemincluding an injector defining a first cavity in fluid communicationwith an orifice configured for needleless injection, a movable member inthe first cavity, the movable member defining a second cavity, and acharge in the second cavity.

[0016] Embodiments include one or more of the following features. Thesecond cavity is at a proximal end of the movable member. The systemfurther includes an electrically conductive member extending at leastpartially across the charge, the electrically conductive member capableof being in electrical communication with a power source. The systemfurther includes a power unit connectable to the injector. The powerunit includes a battery.

[0017] The system can further include a membrane at least partiallyextending across an opening of the second cavity. The system can furtherinclude a first electrically conductive portion connected to the movablemember. The system can further include a second electrically conductiveportion extending through the injector, the second electricallyconductive portion in electrical communication with the firstelectrically conductive portion and capable of being in electricalcommunication with a power source.

[0018] The charge can include at least two discrete materials. The atleast two discrete materials can have different combustioncharacteristics.

[0019] At least a portion of the injector can be disposable.

[0020] The power unit can be reusable.

[0021] The injector can include a needleless injector.

[0022] The moveable member can include a piston.

[0023] In another aspect, the invention features a method of injectionincluding activating a charge in a movable member disposed in aninjector defining an orifice configured for needleless injection.

[0024] Embodiments include one or more of the following features.Activating the charge includes flowing electrical current through thecharge. The charge is disposed in a cavity defined by the movablemember. The cavity is formed at a proximal end of the movable member.The charge includes at least two discrete materials, which can havedifferent combustion characteristics.

[0025] In another aspect, the invention features an injection deviceincluding an injector defining a first cavity and an orifice, a movablemember in the first cavity, a housing defining a second cavity proximalof the movable member, and a charge in the second cavity, the chargeincluding at least two discrete materials.

[0026] Embodiments include one or more of the following features. Thediscrete materials have different combustion characteristics. The chargeincludes at least two layers of materials, which can be adjacent eachother. The charge includes at least one trigger. The charge includes atleast one propellant. The charge includes at least one passive decaymaterial. The charge can be electrically activated.

[0027] The device can further include an electrically conductive memberat least partially extending across the charge.

[0028] The movable member and the housing can be integrally formed.

[0029] The device can be configured for needleless injection.

[0030] The device can include a needleless injector.

[0031] In another aspect, the invention features a method includingigniting a charge in an injector having an orifice so that a fluid in acavity in the injector is ejected out of the cavity, wherein the chargeincludes at least two discrete materials.

[0032] Embodiments include one or more of the following features. Theinjector orifice is configured for needleless injection. The injectorincludes a needleless injector. The method further includes selectingthe at least two discrete materials so that the fluid is ejected fromthe cavity in a predetermined fashion.

[0033] Embodiments can include one or more of the following advantages.The injection systems include injector devices that are resistant tostresses from internal injection pressures produced in the devices.Therefore, the risk of an unreliable injection and/or the risk of dangerto the user can be minimized. In embodiments, the injection pressuresare transmitted directly to a member, e.g., a piston, expelling thefluids such that the fluids are injected predictably, e.g., few, if any,no harmonics in an injection pressure curve.

[0034] In embodiments, the injection devices contain injectable fluidsin a housing that is relatively inert to the injectable fluids. Forexample, the housing can be made of standard,pharmacologically-acceptable materials, such as glass or a polymer.Therefore, the fluids can be maintained efficacious and be deliveredsafely and effectively.

[0035] The injection devices feature a modular, self-containedconfiguration having a compact, low profile. The injection devices arealso easy-to-use, relatively low cost to manufacture, and disposable.

[0036] In some embodiments, the injection systems feature an injectablematerial housing having a relatively small diameter, which can providefor efficient filling during production, e.g., by allowing more housingsto be placed in a manufacturing tray. The design of the housing can alsoprovide a mechanical advantage so that the device is relatively easy touse.

[0037] Embodiments involving a multi-stage charge can exhibit any ofnumerous advantages. As an example, multiple pyrotechnic materials withdifferent burning characteristics can be used in numerous combinations(sequence, stoichiometry, charge shape, particle shape and size, etc) toprovide a desired pressure profile. As another example, the thrust andperformance of the charge can be stable and predictable. As a furtherexample, the charge can be relatively leak-proof, simple andinexpensive. As an additional example, the charge can be relativelyinsensitive to external temperatures. As another example, the charge hasa relatively long shelf life.

[0038] In some embodiments, the injection devices include an injectorthat is resistant to stresses from an internal injection pressureproduced in the devices. Therefore, the risk of an unreliable injectionand/or the risk of danger to the user can be minimized. In someembodiments, the injection pressure is transmitted directly to a memberexpelling the fluids, e.g., a piston, such that the fluids are injectedpredictably, e.g., having no harmonics in an injection pressure curve.

[0039] In some embodiments, the injection devices contain injectablefluids in a housing that is relatively inert to the injectable fluids.For example, the housing can be made of standard,pharmacologically-acceptable materials, such as glass or a polymer.Therefore, the fluids can be maintained efficacious and be deliveredsafely and effectively.

[0040] The injection devices feature a modular, self-containedconfiguration having a compact, low profile. The injection devices arealso easy-to-use, relatively low cost to manufacture, and disposable.

[0041] In some embodiments, the injection devices feature an injectablematerial housing having a relatively small diameter, which can providefor efficient filling during production, e.g., by allowing more housingsto be placed in a manufacturing tray. The design of the housing can alsoprovide a mechanical advantage so that the device is relatively easy touse.

[0042] In general, the invention features an injection device. Thedevice includes: a first housing formed of a first material andconfigured to house an injectable material; a second housing defining anorifice, which is preferably configured for needleless injections, thesecond housing formed of a second material different than the firstmaterial, the first and second housings configured to mate togetherwherein the first housing is capable of transferring the injectablematerial to the second housing, preferably through the orifice that willbe used for injection; and a propellant in the second housing, thepropellant, e.g., a chemical propellant, configured to displace theinjectable material through the orifice and out of the second housing.

[0043] In a preferred embodiment, the injectable material is deliveredto the injector by way of the orifice, which is the same orifice used toinject or to deliver the injectable material.

[0044] In a preferred embodiment, the device includes a first housinghaving an injectable material and a second housing having a propellant,e.g., a chemical propellant. The first housing can be configured suchthat it is detached or left attached to the second housing prior toinjection. The second housing can be proximal to the first housing whenused. In a preferred embodiment, the housings are configured such that,upon mating, a slidable member, e.g., a piston or a stopper, of thefirst housing can be displaced, e.g., in the direction of the secondhousing, to transfer injectable material from the first housing to thesecond housing. The second housing can be configured such that it slidesinto the first housing. In other embodiments, the device includes athird member that displaces a moveable element of the first housing,e.g., the third housing can slide into or over the first housing.

[0045] In a preferred embodiment, the second material: is morebreak-resistant than the first material; comprises a material thatbreaks non-catastrophically; comprises a polymer, e.g., polycarbonate.

[0046] In a preferred embodiment, the first material is chemically inertto the injectable material over a shelf life of the injectable material,e.g., a glass or a polymer.

[0047] In a preferred embodiment, the propellant comprises a chemicalpyrotechnic material. The propellant can be disposed on a moveableelement, e.g., in a movable sleeve. This allows the moveable element tobe displaced from a first position before injection to a second positionafter injection.

[0048] The second housing can comprise a bypass portion and/or alyophilized material, e.g., a protein, in the second housing. The secondhousing further can define a bypass channel configured for transferringthe injectable material from the first housing to the second housing.

[0049] The first housing can comprise two members comprising a resilientand/or compressible material, e.g., butylene rubber and the injectablematerial can be housed between the members.

[0050] The first and second housings can be configured to transferand/or to deliver the injectable material through the orifice.

[0051] In another aspect, the invention features an injection device,comprising: a first housing formed of a first material, e.g., a polymersuch as polycarbonate, and defining an orifice configured for needlelessinjection; a second housing formed of a second material, e.g., glass,different than the first material and configured to house an injectablematerial, the second housing further configured to mate with the firsthousing and to transfer the injectable material to the first housing;and a third housing configured to mate with the second housing and togenerate a pressure in the first housing.

[0052] Embodiments may include one or more of the following features.The first material comprises polycarbonate. The first housing defines abypass channel configured to transfer the injectable material from thesecond housing to the first housing. The injection device furthercomprises a lyophilized material contained in the first housing. Thesecond housing comprises an outer member formed of a third material thatcan be different than the second material. The third material comprisespolycarbonate. The second housing comprises a resilient material, e.g.,a butylene rubber member. The third housing comprises a chemicalpyrotechnic material configured to generate the pressure in the firsthousing. The third housing comprises a movable piston. The third housingcomprises a member extending from an end of the third housing to thefirst housing when the first, second and third housings are fully mated,and the member comprises a movable piston and a chemical pyrotechnicmaterial.

[0053] In another aspect, the invention features a method of using aninjection device, the method comprising: transferring an injectablematerial from a first housing formed of a first material to a secondhousing formed of a second material, the second material being differentthan the first material; and injecting the injectable material byproducing a pyrotechnic reaction in the second housing.

[0054] Embodiments may include one or more of the following features.Transferring the injectable material comprises engaging the secondhousing with the first housing. The method further comprises disengagingthe first housing from the second housing. Transferring the injectablematerial comprises flowing the injectable material through a bypasschannel.

[0055] In another aspect, the invention features an injector,comprising: a housing having a distal end and a proximal end, thehousing defining an orifice configured for needleless injection at thedistal end; a movable member in the housing; and a propellant assemblyconfigured to mate with the proximal end of the housing, wherein theinjector is configured to receive an injectable material through theorifice.

[0056] Embodiments may include one or more of the following features.The housing is configured to mate with a second housing containing theinjectable material from the distal end of the housing. The housing isformed of a material comprising polycarbonate. The housing furtherdefines a bypass channel. The propellant assembly is configured topropel a second movable member using a pyrotechnic reaction. The movablemember is adjacent to the second movable member.

[0057] In yet another aspect, the invention features housing,comprising: a vial having a first end and a second end; a first stopperdisposed at the first end; and a second stopper disposed at the secondend, wherein the vial and the first and second stoppers are configuredto house an injectable material. The second stopper is configured to bemovable in the vial under an applied pressure.

[0058] Embodiments may include one or more of the following features.The vial is formed of a glass. The first and second stoppers, e.g.,formed of a butylene rubber, are configured to be engageable. The firstand/or second stopper comprises a breakable seal.

[0059] In yet another aspect, the invention features an injectiondevice, comprising: a first housing formed of a first material anddefining an orifice, the first housing having a propellant, preferably achemical propellant, therein; a second housing formed of a secondmaterial different than the first material and configured to house aninjectable material, the second housing having a first end and a secondend, wherein the first end is engageable with the orifice; and a memberconfigured to be engageable with the second end, wherein, when the firstand second housings are engaged and the second housing and the memberare engaged, the device is configured to transfer the injectablematerial from the second housing through the orifice to the firsthousing, and the propellant, e.g., a chemical propellant, is configuredto displace the injectable material from the first housing through theorifice.

[0060] Embodiments may contain one or more of the following features.The orifice is configured for needleless injection. The first endcomprises a hollow pin. The first end comprises a butylene memberaffixed to the first end of the second housing. The second end comprisesa member moveable within the second housing. The member composes asleeve having a closed end, the member extending from the closed end.

[0061] In another aspect, the invention features a method of using aninjection device, the method comprising: providing the injection devicecomprising: a first housing formed of a first material and defining anorifice, the first housing having a propellant therein; a second housingformed of a second material different than the first material andconfigured to house an injectable material, the second housing having afirst end and a second end, wherein the first end is engageable with theorifice; and a member configured to be engageable with the second end;engaging the member with the second end; engaging the orifice with thefirst end; and moving the second housing and the member together,wherein the injectable material can be transferred from the secondhousing to the first housing.

[0062] Embodiments may contain one or more of the following features.Engaging the orifice with the first end comprises breaking a seal. Thefirst end comprises a resilient material, e.g., a butylene member havinga hollow pin, and engaging the orifice with the first end comprisesmoving the pin to break a seal on the butylene member. The membercomposes a sleeve having a closed end, the member extending from theclosed end, and moving the second housing and the member togethercomprises moving the second housing coaxially into the sleeve. Themethod further comprises engaging a charge head with the first housing.

[0063] In another aspect, the invention features a method of using aneedleless injection device comprising: providing a first housingdefining an orifice configured for needleless injection; transferring aninjectable material into the first housing through the orifice; andinjecting the injectable material through the orifice.

[0064] Embodiments may contain one or more of the following features.Injecting the material comprises reacting a chemical pyrotechnicmaterial. Transferring the material comprises engaging the first housingwith a second housing configured to house the material. Transferring thematerial further comprises displacing a member in the second housing.Transferring the material further comprises engaging the second housingwith a third housing.

[0065] In another aspect, the invention features a method of providingan injection device comprising: providing a first housing formed of afirst material and configured to house an injectable material; providinga second housing defining an orifice, the second housing formed of asecond material different than the first material, the first and secondhousings configured to mate together wherein the first housing iscapable of transferring the injectable material to the second housing,the second housing having a propellant, e.g., a chemical propellant,configured to displace the injectable material through the orifice andout of the second housing; and mating the first and second housingstogether.

[0066] Embodiments may contain one or more of the following features.The method further comprises transferring the injectable material fromthe first housing to the second housing through the orifice. The methodfurther comprises injecting the injectable material through the orifice.

[0067] In yet another aspect, the invention features a method ofproviding an injection device comprising: providing a first housingformed of a first material and configured to house an injectablematerial; providing a second housing defining an orifice, the secondhousing formed of a second material different than the first material,the first and second housings configured to mate together wherein thefirst housing is capable of transferring the injectable material to thesecond housing, the second housing having a propellant configured todisplace the injectable material through the orifice and out of thesecond housing; and optionally providing instructions for using theinjection device. In another embodiment, the method further comprisesplacing the injectable material in the first housing.

[0068] In another aspect, the invention features a method of providing aneedleless injection device powered by a chemical propellant, e.g., apyrotechnic material or a propellant that undergoes a chemical reactionto produce a gas. The method can include providing, e.g., manufacturing,a first housing as described herein; providing, e.g., manufacturing, asecond housing as described herein; and optionally, combining the firstand second housings or providing instructions to another entity tocombine them.

[0069] In a preferred embodiment, one compound, e.g., a liquid, e.g., adiluent, is disposed in one housing, and a second compound, e.g., a drycompound, e.g., a lyophilized material, is disposed in another housing.In a preferred embodiment, both compounds are disposed in one housing.

[0070] In a preferred embodiment, a first entity places a firstcompound, e.g., a diluent, in one housing, and a second entity places asecond compound, e.g., a lyophilized material, in another housing. In apreferred embodiment, one entity places a first compound in a firsthousing and places a second compound in a second housing.

[0071] In a preferred embodiment, one or both of the first and secondentities provide instructions to a third entity, e.g., a healthcareprovider or a patient, to combine the first and second housings.

[0072] As used herein, “injectable material” refers to any material ormixture of materials that can be injected into the body of a subject,e.g., a human or an animal. For example, an injectable material can be afluid, e.g., a diluent or a diluent and a drug.

[0073] Other features, objects, and advantages of the invention will beapparent from the description and drawings, and from the claims.

DESCRIPTION OF DRAWINGS

[0074]FIG. 1 is a perspective view of an embodiment of an injectionsystem.

[0075]FIG. 2 is a perspective view of an embodiment of an injectordevice.

[0076]FIG. 3 is a perspective view of an embodiment of a fluid transferdevice.

[0077]FIG. 4 is a side view of the injection system of FIG. 1.

[0078]FIG. 5 is a cross sectional view of the injection system of FIG.1.

[0079]FIG. 6 is an exploded perspective view of the fluid transferdevice of FIG. 3.

[0080]FIG. 7 is an end view of the fluid transfer device of FIG. 3.

[0081]FIG. 8 is a cross sectional view of the fluid transfer device ofFIG. 7, taken along line 8-8.

[0082]FIG. 9 is a cross sectional view of the fluid transfer device ofFIG. 7, taken along line 9-9.

[0083]FIG. 10 is an exploded perspective view of an embodiment of aninjector device.

[0084]FIG. 11 is an end view of the injector device of FIG. 10.

[0085]FIG. 12 is a cross sectional view of the injector device of FIG.11, taken along line 12-12.

[0086]FIG. 13 is a cross sectional view of the injector device of FIG.11, taken along line 13-13.

[0087]FIG. 14 is an end view of an embodiment of an injector device.

[0088]FIG. 15 is a cross sectional view of the injector device of FIG.14, taken along line 15-15.

[0089]FIG. 16 is a cross sectional view of the injector device of FIG.14, taken along line 16-16.

[0090]FIG. 17 is a perspective view of an embodiment of a charge cup.

[0091]FIG. 18 is an end view of an embodiment of an injector device.

[0092]FIG. 19 is a cross sectional view of the injector device of FIG.18, taken along line 19-19.

[0093]FIG. 20 is a cross sectional view of the injector device of FIG.18, taken along line 20-20.

[0094]FIG. 21 is an end view of an embodiment of an injection system.

[0095]FIG. 22A is a schematic cross sectional view of the injectionsystem of FIG. 21, taken along line 22A-22A.

[0096]FIG. 22B is a schematic cross sectional view of the injectionsystem of FIG. 21, taken along line 22B-22B.

[0097]FIG. 23 is an exploded perspective view of the injection system ofFIG. 21.

[0098]FIGS. 24A, 24B, 24C, and 24D are cross sectional views of theinjector system of FIG. 21 during use.

[0099]FIG. 25 is an end view of an embodiment of an injector device.

[0100]FIG. 26 is a cross sectional view of the injector device of FIG.25, taken along line 26-26.

[0101]FIG. 27 is a cross sectional view of the injector device of FIG.25, taken along line 27-27.

[0102]FIG. 28 is a detailed view of the injector device of FIG. 26.

[0103]FIG. 29 is an exploded perspective view of the injector device ofFIG. 26.

[0104]FIG. 30 is an illustrated plot of pressure as a function of timefor a relatively fast burning material.

[0105]FIG. 31 is an illustrated plot of pressure as a function of timefor a relatively slow burning material.

[0106]FIG. 32 is an illustrated plot of pressure as a function of timefor a combination of relatively fast and slow burning materials.

[0107]FIG. 33 is a schematic cross sectional view of an embodiment of aloaded charge cup.

[0108]FIG. 34 is a perspective view of an embodiment of an injectionsystem.

[0109]FIG. 35 is an exploded perspective view of the injector system ofFIG. 34.

[0110]FIG. 36 is an end view of the injector system of FIG. 34 FIG. 37is a cross sectional view of the injector system of FIG. 36, taken alongline 37-37.

[0111]FIG. 38 is a cross sectional view of the injector system of FIG.36, taken along line 38-38.

[0112]FIG. 39 is a plot of pressure as a function of time for anembodiment of a charge.

[0113]FIG. 40 is a plot of pressure as a function of time for anembodiment of a charge.

[0114]FIG. 41 is a plot of pressure as a function of time for anembodiment of a charge.

[0115]FIG. 42 is a plot of pressure as a function of time for anembodiment of a charge.

[0116]FIG. 43 is a plot of pressure as a function of time for anembodiment of a charge.

[0117]FIG. 44 is a plot of pressure as a function of time for anembodiment of a charge.

[0118]FIG. 45 is a plot of pressure as a function of time for anembodiment of a charge.

[0119]FIG. 46 is a plot of pressure as a function of time for anembodiment of a charge.

[0120]FIG. 47 is a plot of pressure as a function of time for anembodiment of a charge.

[0121]FIG. 48 is a plot of pressure as a function of time for anembodiment of a charge.

[0122]FIG. 49 is a plot of pressure as a function of time for anembodiment of a charge.

[0123]FIG. 50 is a plot of pressure as a function of time for anembodiment of a charge.

[0124]FIG. 51 is a plot of pressure as a function of time for anembodiment of a charge.

[0125]FIG. 52 is a plot of pressure as a function of time for anembodiment of a charge.

[0126]FIG. 53 is a plot of pressure as a function of time for anembodiment of a charge.

[0127]FIG. 54 is a plot of pressure as a function of time for anembodiment of a charge.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0128] The invention relates to injection systems and devices that canbe used in injection systems.

[0129] Referring to FIGS. 1-5, a needleless injection system 50 includesan injector device 52 and a fluid transfer device 54. Injector device 52and fluid transfer device 54 are configured to mate with each other(FIGS. 1, 4 and 5). Generally, fluid transfer device 54 contains aninjectable fluid 56, such as an aqueous diluent, e.g., a salinesolution, and another material 58, such as a lyophilized material,separate from the injectable fluid (FIG. 5). Injector device 52, whichcontains a multi-component charge system, is configured to receiveinjectable fluid 56 and material 58 from fluid transfer device 54, andto inject mixed fluid and material to a subject, e.g., a human.

[0130] Fluid transfer device 54 is generally configured to house one ormore injectable materials, e.g., fluid 56 and material 58. Referring toFIGS. 6-9, device 54 includes a vial 60, here, a cylindrical tube madeof a material that is stable and substantially inert to fluid 56 andmaterial 58 for extended periods of time, e.g., over the shelf life ofthe injectable material. Typically, the material for vial 60 isrelatively rigid and relatively impervious to diffusion and evaporation,such that, for example, fluid 56 does not leach out of the vial.Materials include, for example, those that are FDA-approved and/or thoseused for pharmacological purposes, such as glass, polymers, andmetal-containing materials.

[0131] Typically, vial 60 contains therein four stoppers that defineseparate cavities for fluid 56 and material 58. Starting at its top orproximal end, vial 60 includes a top stopper 62, a first middle stopper64, a second middle stopper 66, and a bottom stopper 68 located at thebottom or distal end of the vial. Top stopper 62 includes a centrallypositioned top needle 70, e.g., a stainless steel or relatively hardplastic needle, and a pierceable portion 72 adjacent to the bottom ordistal end of the top needle. At its top or proximal end, top needle 70is configured to engage with an orifice of injector device 52 (describedbelow). First and second middle stoppers 64 and 66 are connectedtogether by a middle needle 74. At its distal end, middle needle 74 issecured to second middle stopper 66; and at its proximal end, the middleneedle is adjacent to a pierceable portion 76 of first middle stopper64. Bottom stopper 68 seals the distal end of vial 60 and is configuredto engage with a pushrod (described below). Thus, referring particularlyto FIGS. 8 and 9, top stopper 62 and first middle stopper 64 define afirst cavity that houses material 58; and second middle stopper 66 andbottom stopper 68 define a separate second cavity that houses fluid 56.

[0132] In general, stoppers 62, 64, 66, and 68 can be made of anymaterial that can provide a good seal, e.g., a liquid-tight and/orair-tight seal, with vial 60. As an example, a suitable stopper materialis a resilient material such as butylene rubber. Typically, the stoppersshould be movable within vial 60 while still providing a good seal withthe vial. In embodiments, stoppers 62, 64, 66, and 68 can be made of thesame material or different materials.

[0133] Fluid transfer device 54 further includes an adaptor 78 and abase 80. Adaptor 78 is configured to receive and to secure the proximalend of vial 60 so that fluid transfer device 54 can engage with injectordevice 52. Adaptor 78 can include one or more tangs 82 that enhanceconnection to and release from injector device 52. Base 80 is configuredto receive the distal or bottom end of vial 60. Base 80 includes anintegrally formed pushrod 84 that can engage with bottom stopper 68during use (described below).

[0134] Other embodiments of fluid transfer devices are possible and aredescribed in U.S. Provisional Patent Application Serial Nos. 60/250,410;60/250,425; 60/250,537; and 60/250,573, all filed on Nov. 30, 2000, andall entitled “Injection Devices”, the entire contents of which are allhereby incorporated by reference. For example, in embodiments, a fluidtransfer device may include only two stoppers that define a cavity for afluid only, as described in U.S. Ser. No. 60/250,573. In embodiments, afluid transfer device may include a material housed in a stopper andsealed in a powder pack, as described in U.S. Ser. No. 60/250,410.Combinations of such embodiments can be used.

[0135] Injector device 52 is generally configured to receive injectablematerial (fluid 56 and material 58) transferred from fluid transferdevice 54 and to deliver the material to a subject. As described below,numerous embodiments of injector device 52 are possible.

[0136] Referring to FIGS. 10-13, in some embodiments, an injector device100 includes a multi-component charge that is activated electrically,here, with a two-lead design. Injector device 100 generally includes,starting distally, an injector 102, an injector cap 104, and a batterycap 106 located proximally. Injector 102, injector cap 104, and batterycap 106 are attached coaxially by threaded connections 108 and 110.Injector 102 defines a chamber 112, here, a generally elongatedcylindrical cavity, that receives injectable material, and an orifice114 (in fluid communication with chamber 112) through which theinjectable material is delivered to the chamber and expelled during use.Orifice 114 is generally configured for needleless injection. Injector102 is generally made of a material that is more break-resistant thanthe material of vial 60. Preferably, the material of injector 102 isresistant to mechanical shock from discharge of the charge, e.g., theinjector material has a burst strength greater than the pressuregenerated by the charge (as described below). The material of injector102 preferably fails non-catastrophically, e.g., does not shatter, ifexposed to sufficient mechanical shock. Suitable materials for injector102 include, for example, polycarbonates and polysulfones.

[0137] Inside injector 102 and injector cap 104, device 100 includes apiston 116, a charge sleeve 118, and a charge cup 120. In general,during use, piston 116 and charge sleeve 118 are slidably movable withininjector 102, while charge cup 120 is fixedly secured between theinjector and injector cap 104 (FIGS. 12 and 13). Piston 116 includes anO-ring 122 and a backup ring 124 that provide a tight, but movable, sealbetween the piston and the wall of chamber 112. Similarly, charge cup120 includes an O-ring 126 and a backup ring 128 that provide a tightseal between the charge cup and charge sleeve 118, while still allowingthe charge sleeve to slide within injector 102. Charge cup 120 furtherdefines a charge cavity 130 in which the charge is placed. After thecharge is loaded in cavity 130, the charge is covered and sealed with aburst membrane 132 and covered with a nozzle 134. Burst membrane 132 canbe, for example, a 0.005 inch thick disc of Mylar® foil. Nozzle 134,which fits over a portion of charge cup 120, is a cylindrical cup havingan opening at its base. Nozzle 134 provides a good interference fitbetween charge cup 120 and charge sleeve 118, and can also minimize anybulging of the charge cup near cavity 130 due to packing of the chargein the cavity. Piston 116 and charge cup 120 can be made of, e.g.,injection molded polymer such as polycarbonate. Nozzle 134 and chargesleeve 118 can be made of, e.g., stainless steel.

[0138] In some embodiments, the charge includes a mixture of apropellant (e.g., 1:1 copper oxide and 5-aminotetrazole, or 5AT) and atriggering material (e.g., sucrose and potassium chlorate). Numerousother systems can be used. Generally, specific compositions for chargesystems are determined empirically, taking into account, for example,the size of the injector, the amount of injectable material to bedelivered, and the size of the orifice. A non-limiting, illustrativelist of examples of chemical components that can be used are disclosedin U.S. Pat. Nos. 4,103,684; 4,342,310; 4,447,225; 4,518,385; 4,592,742;4,623,332; 4,680,027; 4,722,728; 4,913,699; 5,024,656; 5,049,125;5,064,123; 5,190,523; 5,304,128; 5,312,335; 5,334,144; 5,383,851;5,399,163; 5,499,972; 5,501,666; 5,503,628; 5,520,639; 5,569,189;5,630,796; 5,704,911; 5,730,723; 5,840,061; 5,851,198; 5,879,327;5,899,879; 5,899,880; 5,911,703 and 5,993,412, each of which is herebyincorporated by reference.

[0139] As mentioned above, injector device 100 electrically activates orignites the charge. Charge cup 120 further includes two wire leads 136connectable to an electrical energy source. Leads 136 extend from cavity130 (and the charge) to an energy source, here, a battery 138. Battery138, e.g., a lithium coin battery, is secured between injector cap 104and battery cap 106. Battery 138 is nested in an electrically-conductingcontact can 140 along with a cushion disc 142 made of a resilientmaterial. Contact can 140 has a rim configured to contact one terminalof battery 138, and an opening 144 that allows one of leads 136 tocontact another terminal of the battery. Cushion disc 142 can minimizerecoil during use of injector device 100 and allows battery 138 to bedepressed to contact one of the leads 136 (described below).

[0140] Turning now to leads 136, at their distal ends, the leadsterminate near charge cavity 130. Leads 136 can terminate anywhere alongthe longitudinal length of cavity 130, depending on which part of thecharge is to be exposed to activation or ignition. The distal ends orportions of leads 136 are electrically connected together, e.g., by atungsten filament (not shown) that extends across cavity 130, e.g.,transverse to the longitudinal length of the cavity. In someembodiments, the surface of cavity 130 can be coated with anelectrically-conducting layer, and the distal portions of leads 136 canbe electrically connected together via the electrically-conductinglayer. At their proximal ends, one of leads 136 contacts contact can140, and the other one of the leads extends through opening 144 and isslightly spaced from a terminal of battery 138 (FIG. 12).

[0141] In operation, injectable material, i.e., fluid 56 and material58, is transferred from fluid transfer system 54 to injector device 100;the system and the device are separated; and the injectable material isejected from the injector device. Referring again to FIG. 5, injector102 and adaptor 78 are connected together, e.g., snap fit together.Orifice 114 and top needle 70 are engaged in fluid communication witheach other.

[0142] With fluid transfer device 54 and injector device 100 connected,the injector device is pushed down or distally, with base 80 stationary,e.g., against a fixed, flat surface. As pressure develops in vial 60 toa sufficient or predetermined level, top needle 70 pierces pierceableportion 72, and middle needle 74 pierces pierceable portion 76. Asinjector device 100 is pushed down, pushrod 84 advances bottom stopper68 up. As injector device 100 is continued to be pushed down, fluid 56is transferred through middle needle 74 to the cavity between topstopper 62 and first middle stopper 64 where the fluid mixes withmaterial 58. The mixed material is transferred through top needle 70,through orifice 114, and into chamber 112. Injector device 100 isadvanced down until a predetermined amount of fluid 56, material 58,and/or mixed material are transferred to the injector device, at whichtime the injector device is disconnected from fluid transfer device 54.

[0143] To inject the mixed material from injector device 100, orifice114 is placed adjacent to a predetermined injection site, and battery138 is pushed distally or down. As battery 138 is pushed down, one ofits terminals contacts the spaced proximal end of one of the leads 136(FIG. 12), thereby completing an electrical loop between the leads 136(since the other lead is already connected to the other terminal of thebattery via contact can 140). Electrical energy from battery 138 flowsthrough the filament extending across the charge, and ignites thecharge. The activated or ignited charge generates gas, i.e., pressure,in cavity 130. The gas ruptures burst membrane 132 at a predeterminedpressure and propels charge sleeve 188 and piston 116 distally, therebypushing the injectable material through orifice 114 and into theinjection site.

[0144] FIGS. 14-16 show another embodiment of an injector device 150, inwhich elements similar to elements described above are designated withthe same reference characters. Injector device 150 includes a separatecup 152 for housing the charge and a modified arrangement of wire leads.Cup 152 further minimizes any bulging of charge cup 120 due to packingof the charge. Cup 152 allows the charge to be prepared separately fromcharge cup 120. Cup 152 also allows the charge to be prepared modularly,e.g., like tailorable bullet modules that can be loaded intopredetermined injector devices according to medication, dosage, deliveryrate, etc.

[0145] Referring particularly to FIG. 17, cup 152 includes two slots 154and two grooves 156. Slots 154 are configured to receive a wire or afilament (not shown) that extends across the longitudinal length of cup152 and through the charge. The wire, e.g., a tungsten filament, can besecured to cup 152 with an electrically-conducting material, such as anelectrically-conducting epoxy. Slots 154 are also designed so that thewire or filament can be relatively easily threaded and attached to cup152. Grooves 156 extend along the side of cup 152 and to the bottom ofthe cup (FIG. 15). Grooves 156 and the top surface or rim 160 of cup 152are coated with an electrically-conducting layer, e.g., a metal layer,such that the layer can electrically contact the wire or filament. Thus,electrically-conducting material in one of the grooves 156 at the bottomof cup 152 is in electrical communication with electrically-conductingmaterial in another one of the grooves at the bottom of the cup via thegrooves on the side of the cup, rim 160, and the wire or filament. Inother embodiments, cup 152 can have more than two slots 154 and/orgrooves 156 that can be arranged in different arrangements, e.g.,asymmetrically arranged around the cup.

[0146] Referring particularly to FIG. 15, injector device 150 furtherincludes two wire leads 158. At their distal ends, one of the leads 158electrically contacts electrically-conducting material formed in one ofthe grooves 156 at the bottom of cup 152, and the other lead contactselectrically-conducting material formed in the other groove 156 at thebottom of the cup. At their proximal ends, one of the leads 158 contactscontact can 140, and the other lead is spaced from battery 138, asdescribed above. In use, injectable material is transferred to injectordevice 150 and ejected from the device as generally described above.

[0147] FIGS. 18-20 show another embodiment of an injector device 170, inwhich elements similar to elements described above are designated withthe same reference characters. Injector device 170 is generally similarto injector device 100, but modified to include one center lead 172instead of two leads 136. At its proximal end, lead 172 contacts aterminal of a battery assembly 174, here, two lithium coin batteries. Atits distal end, lead 172 extends through cavity 130, and a distalportion of the lead is crimped to an electrically-conducting filament176 by an electrically-conducting tube 178. Filament 176 extends throughthe charge in cavity 130, between burst membrane 132 and the distal endof charge cup 120, and between the charge cup and nozzle 134 where thefilament contacts a contact strip 180. Contact strip 180 also contactscharge sleeve 118. Electrical contact is continued from contact strip180 to a second contact strip 182, for example, by making charge sleeve118 out of an electrically-conducting material such as stainless steelor by connecting the contact strips with a filament. Second contactstrip 182 is capable of contacting a second terminal of battery assembly174. For example, second contact strip 182 can be connected to contactcan 140, e.g., by a filament, and the contact can may have a portionthat is spaced from, but capable of contacting, the second terminal ofbattery assembly 174. The portion can be contacted with the secondterminal, e.g., by depressing a button 184 and cushion disk 142. Device170 can be triggered by depressing button 184, which completes anelectrical loop to ignite the charge.

[0148]FIGS. 21, 22A, 22B, and 23 show another embodiment of an injectionsystem 200 wherein a fluid transfer device is integrated with aninjector device. Elements similar to elements described above aredesignated with the same reference characters. System 200 includes aninjector 202, an injector cap 204, and a removable safety band 206.Injector 202 defines a chamber 210 and an orifice 212, as generallydescribed above. In some embodiments, chamber 210 contains an injectablematerial, such as a lyophilized material. In some embodiments, chamber210 is empty. Injector 202 and injector cap 204 are movable relative toone another by a threaded connection 208 when safety band 206 is removedfrom system 200, e.g., by a user.

[0149] Within injector 202 and injector cap 204, system 200 includes apiston 214, a vial 216, and a charge cup 218. Piston 214 includes anO-ring 220 and a backup ring 222, as generally described above. Piston214 defines a lumen 224 that extends transverse to the length of thepiston, and an annular tab 225. Tab 225 engages a portion of injector202 to keep piston 214 stationary when fluid is transferred through thepiston (described below). Tab 225 is also configured to separate, e.g.,shear, from piston 214 under a predetermined force, e.g., a force ofinjection. Disposed within piston 214 is a piercing element 226, e.g., ahollow needle, that is in fluid communication with lumen 224 and extendsproximally where it engages a stopper seal 227. Stopper seal 227 sealsthe proximal end of piercing element 226. For example, in embodiments inwhich chamber 210 contains a material, such as a sprayed dried orlyophilized powder, stopper seal 227 can be used with piston 214 to sealthe chamber to protect the material from exposure, e.g., to air. Orifice212 can be sealed with a removable barrier. Vial 216, e.g., a glass vialas described above, is coaxially positioned within injector 202.

[0150] Within vial 216 are a distal stopper 228 and a proximal stopper230 that contain an injectable fluid 232 therebetween. Distal stopper228, e.g., made of a biocompatible or inert material, such a butylrubber, includes a pierceable portion 234 adjacent to stopper seal 227.Proximal stopper 230 includes an outer portion 229 and an inner core231. In some embodiments, outer portion 229 and inner core 231 areformed of different materials. For example, outer portion 229 can beformed of a material, e.g., a butyl rubber, that is relatively inert tofluid 232 and provides a tight seal with vial 216; and core 231 can beformed of a relatively rigid material having a relatively highdurometer. Core 231 can provide system 200 with predictable injections,e.g., by minimizing undesirable harmonics during injection. Charge head218, including embodiments for igniting the charge, can be any of theembodiments described above and below, for example, as in injectordevice 100, 150, or 170.

[0151] FIGS. 24A-24D show one embodiment of a method of using injectionsystem 200. Safety band 206 is removed to allow injector cap 204 to berotated to advance the injector cap toward orifice 212, i.e., distally.As injector cap 204 advances distally, distal and proximal stoppers 228and 230 are also forced distally such that piercing element 226 piercesstopper seal 227 and portion 234 of the distal stopper (FIG. 24B). Tab225 keeps piston 214 generally stationary. As the injector cap isadvanced further, fluid 232 is transferred from between stoppers 228 and230, through piercing element 226, through lumen 224, and into chamber210, where, in some embodiments, the fluid mixes with another material,e.g., a lyophilized material. Injector cap 204 is advanced distallyuntil all of fluid 232 is transferred into chamber 210 (FIG. 24C).Distal stopper 228 mates with piston 214. Injectable material, i.e.,fluid 232 or fluid mixed with another material, is expelled throughorifice 212 by triggering charge head 218 as described above. Triggeringthe charge head propels the charge sleeve distally, which propelsstoppers 228 and 230 and piston 214 distally (and shears tab 225),thereby expelling the injectable material through orifice 212 (FIG. 24D)

[0152] In some embodiments, proximal stopper 230 can be made of onematerial, e.g., integrally formed of one material. Distal stopper 288can be formed of multiple materials, as described above for stopper 230.In certain embodiments, e.g., in which only a fluid is injected, e.g.,no lyophilized material, stopper seal 227 and distal stopper 228 can beintegrally formed as one component. In such embodiments, stopper seal227 and stopper 228 can be formed of the same or different materials. Inembodiments, piston 214 and piercing element 226 can be integrallyformed. For example, piston 214 can define a proximal piercing portioncapable of piercing stopper seal 227 and distal stopper 228. Theproximal piercing portion is capable of establishing fluid communicationbetween lumen 224 and material 232. Other configurations of lumen 224are possible to transfer material 232 from one end of piston 214 toanother end.

[0153] FIGS. 25-29 show another embodiment of an injector device 250 inwhich the charge is ignited non-electrically, here, chemically. Device250 includes an injector 252, an injector cap 254 connected to theinjector by a threaded connection 258, and a safety cap 256. Injector252 defines an orifice 260 and a chamber 262 for injectable material,generally as described above.

[0154] Within injector 252 and injector cap 254, device 250 includes apiston 264 and a charge cup 266. Piston 264 includes a piston O-ring 268and a piston backup ring 270; and charge cup 266 includes a charge cupO-ring 272 and a backup ring 274, as generally described above. Chargecup 266 defines a charge cavity 282, a breakable capsule 284, and aburst membrane 286. As described below, charge cavity 282 contains acharge, and capsule 284 contains a material capable of activating origniting the charge, e.g., a catalyst or an oxidizing agent such assulfuric acid.

[0155] Proximal of piston 264, device 250 further includes a shear pin276, a movable charge sleeve 278, and a nozzle 280. Shear pin 276 holdscharge sleeve 278 stationary at an initial position until apredetermined pressure is generated by the charge. Charge sleeve 278includes a projection 288 that abuts against burst membrane 286 andcapsule 284 (FIG. 28). Device 250 also includes a gasket 294 that,during use, minimizes recoil and allows safety cap 256 to be advanceddistally (described below).

[0156] Safety cap 256 includes a removable safety tab 292, e.g., a stripof plastic. Safety cap 256 is attached to device 250 by a threadedconnection 290 defined by the proximal end of charge cup 266.

[0157] In operation, device 250 is fired by removing safety tab 292 fromthe device, which allows safety cap 256 to be pushed distally, towardorifice 260, which is abutted against a surface, e.g., a subject's skin.As safety cap 256 is pushed distally (by a distance approximately equalto the thickness of safety tab 292 via threaded connection 290),projection 288 deforms burst membrane 286 and breaks capsule 284,thereby releasing the activating or igniting material inside thecapsule. The activating material reacts with the charge in cavity 282and generates pressure. The pressure increases inside cavity 282 untilburst membrane 286 ruptures and the force against charge sleeve 278 issufficient to break shear pin 276. This pressure moves sleeve 278distally, thereby pushing piston 264 distally and expelling injectablematerial in chamber 262 through orifice 260.

[0158] FIGS. 34-38 show another embodiment of an injection system 350including an injector device 352 and a power unit 354. Injector device352 can be disposable, and power unit 354 can be reusable.

[0159] Referring particularly to FIG. 35, injector device 352 includesan injector 356 and an injector cap 358 connectable to the injector by athreaded connection and sealable with a face seal 361, e.g., an O-ring.Injector 356 defines a cavity 359 and an orifice 362, as generallydescribed above. Within injector 356 and cap 358, injector device 352includes a piston 360, an electrically-conductive bridge 364 thatengages the proximal end of the piston, and a membrane 367, e.g., a discof paper, between the piston and injector cap 358. Piston 360 includesO-rings 368 and backup rings 370, and defines a charge cavity 366 at theproximal end, as generally described herein. That is, charge cavity 366is integrally formed with piston 360. Bridge 364 includes two conductivemembers 372 that fit into two grooves 374 defined by piston 360. A wire376, e.g., a tungsten filament, extends from one member 372, through acharge in cavity 366, and to the other member 372. Injector device 352further includes two electrically-conductive leads 378 that extend frommembers 372 and through injector 356 to contact power unit 354.

[0160] Power unit 354 includes an adaptor 380, a battery 382, and aswitch 384. Adaptor 380 is configured to connect to injector device 352and to trigger the injector device. Numerous embodiments are possible.In some embodiments, adaptor 380 includes two extensions 386 that engagewith injector device 352 (FIG. 34). Each extension 386 has a conductivelead 388 therein that extends from lead 378 to battery 382, where theleads are capable of contacting a terminal of the battery. Switch 384 isconfigured to selectably connect the terminals of battery 382 to leads388, thereby passing a current through the leads. For example, a springcan be placed between injector cap 358 and battery 382 to push batteryproximally, and by depressing switch 384 distally, the terminals of thebattery can be urged distally into contact with leads 388. Otherembodiments of switch 384 are possible.

[0161] In operation, an injectable material (not shown) is placed cavity359, and orifice 362 is placed adjacent to an injection site. Switch 384is then activated such that an electrical current flows from battery 382and through leads 388, leads 378, members 372, and filament 376. Thecurrent flowing through filament 376 ignites the charge in cavity 366.The ignited charge generates pressure as described herein and propelspiston 360 distally, thereby ejecting the injectable material out ofcavity 359, through orifice 362, and into the injection site. Afterinjection, injection device 352 can be disconnected from power unit 354,and another injection device can be connected to the power unit.

[0162] Other embodiments of injector devices are possible and aredescribed in incorporated-by-reference U.S. Provisional PatentApplication Serial Nos. 60/250,410; 60/250,425; 60/250,537; and60/250,573.

[0163] The injectable material can include one or more substances. Forexample, the second substance can be a liquid, e.g., a diluent orsolute. Such liquids can include buffers, inert fillers,pharmaceutically acceptable carriers, or the like.

[0164] The substance can be a dry substance, e.g., a lyophilizedprotein, nucleic acid, e.g., RNA or DNA, or polysaccharide. Thesubstance can be a vaccine, or a drug. The substance can be a peptide,polypeptide, or protein, e.g., an antibody, an enzyme, a hormone orgrowth factor. Preferred substances include insulin. The substance canbe: a blood protein, e.g., clotting factor VIII or a IX, complementfactor or component; a hormone, e.g., insulin, growth hormone, thyroidhormone, a catecholamine, a gonadotrophin, PMSG, a trophic hormone,prolactin, oxytocin, dopamine and the like; a growth factor, e.g., EGF,PDGF, NGF, IGF's and the like; a cytokine, e.g., an, interleukin, CSF,GMCSF, TNF, TGF-alpha, TGF-beta. and the 25 like; an enzyme, e.g.,tissue plasminogen activator, streptokinase, cholesterol biosynthetic ordegradative, glycosolases, and the like; a binding protein, e.g., asteroid binding protein, a growth hormone or growth factor bindingprotein and the like; an immune system protein, e.g., an antibody, SLAor MHC gene or gene product; an antigen, e.g., a bacterial, parasitic,or viral, substance or generally allergens and the like. The substancescan be combined by the subject, or by another person.

[0165] The subject can be a human or an animal, e.g., a laboratoryanimal, or pet, e.g., a dog or cat, or other animal, e.g., a bovine, aswine, a goat, or a horse.

[0166] Therapeutic agents that can be used in the devices and methodsdescribed herein include, for example, vaccines, chemotherapy agents,pain relief agents, dialysis-related agents, blood thinning agents, andcompounds (e.g., monoclonal compounds) that can be targeted to carrycompounds that can kill cancer cells. Examples of such agents include,insulin, heparin, morphine, interferon, EPO, vaccines towards tumors,and vaccines towards infectious diseases.

[0167] The device can be used to deliver a therapeutic agent to anyprimate, including human and non-human primates. The device can be usedto deliver an agent, e.g., a therapeutic agent to an animal, e.g., afarm animal (such as a horse, cow, sheep, goat, or pig), to a laboratoryanimal (such as a mouse, rat, guinea pig or other rodent), or to adomesticated animal (such as a dog or cat). The animal to which thetherapeutic agent is being delivered can have any ailment (e.g., canceror diabetes). It is expected that the device may be most useful intreating chronic conditions. However, the device can also be used todeliver a therapeutic agent (such as a vaccine) to an animal that is notsuffering from an ailment (or that is suffering from an ailmentunrelated to that associated with the therapeutic agent). That is, thedevice can be used to deliver therapeutic agents prophylactically.

[0168] The devices and methods of the invention can be used toindividually tailor the dosage of a therapeutic agent to a patient.

[0169] The devices and methods of the invention can allow for outpatienttreatment with increased convenience, such as, for example, without theuse of an I.V.

[0170] Devices and methods described herein can be advantageous becausethey can be used to promote maintenance of the concentration of atherapeutic agent in a patient's plasma within a safe and effectiverange. Moreover, the device can release therapeutic agents in responseto the concentration of an analyte in the patient's system. Thus, therate of drug delivery can be appropriate for the patient's physiologicalstate as it changes, e.g., from moment to moment.

The Charge

[0171] In general, the charge is formed of at least two discretematerials (e.g., at least two discrete materials, at least threediscrete materials, at least four discrete materials, at least fivediscrete materials, at least six discrete materials, at least sevendiscrete materials, at least eight discrete materials, at least ninediscrete materials, at least 10 discrete materials, at least 11 discretematerials, at least 12 discrete materials, at least 13 discretematerials, at least 14 discrete materials, at least 15 discretematerials, at least 16 discrete materials, at least 17 discretematerials, at least 18 discrete materials, at least 19 discretematerials, at least 20 discrete materials) formed as separatecomponents. The discrete materials are typically used in combination toprovide a desired pressure profile of the injectable fluid ejected by aninjection device. Each discrete material can be formed of a singlematerial or a combination of materials. In embodiments, by combining thediscrete materials in a predetermined assembly or sequence, with apredetermined macroscopic shape(s), and/or with a predeterminedmicroscopic structure(s), such as spheres or rods, the charge canpropel, e.g., a piston with a predetermined pressure profile, i.e.,pressure as a function of time. Accordingly, the piston can inject theinjectable material from an injector with the predetermined pressureprofile capable of injecting the injectable material effectively.

[0172] In general, the types of discrete materials used in a charge caninclude, for example, one or more triggers (a discrete material capableof generating relatively large amounts of gas and heat), one or morepropellants (a relatively slow burning material) and/or one or morepassive decay materials (a low-yielding material that continues the burnof the charge but which does not add a substantial amount of heat orkinetic effect).

[0173] In general, the order of the discrete material used in a chargecan be varied as desired. As an example, a charge can have one or morepropellants disposed between one or more triggers and one or morepassive decay materials. As another example, a charge can have one ormore triggers disposed between one or more propellants and one or morepassive decay materials. As another example, a charge can have one ormore passive decay materials disposed between one or more triggers andone or more propellants. As a further example, one or more propellantscan be intercalated with one or more triggers and/or one or more passivedecay materials. Combinations of these exemplary embodiments can beused. For example, in certain embodiments, a charge includes two or morediscrete pyrotechnic materials that can react and deflagrate. Eachpyrotechnic material can be formed of a single material or a combinationof materials. Deflagrations can proceed at any desired rate (e g.,several inches per second, several hundred feet per second). Examples ofreactions that undergo deflagrations include those used in air bagchemistry and rocket motor chemistry.

[0174] Typically, the charge is designed so that it is capable ofgenerating pressure such that the injectable material can be ejected byan injection device with sufficient force to create an opening in thebody (e.g., an opening in the skin of the body) through which theinjectable material can be injected (FIG. 30). The opening can created,for example, relatively quickly and acceptably small to minimize painand discomfort to the body. For example, in certain embodiments, thetrigger can be capable of generating a relatively high initial pressure,such as about 4,000 psi, in a relatively short amount of time, such asabout 1-5 msec, e.g., 1-2.5 msec. In some embodiments, the pressureprofile of the trigger can have duration or latency of, for example,about 15 msec, with a final pressure of about 500 psi. In embodiments,the charge can be capable of generating sufficient pressure such thatthe injectable material can continue to keep the opening open so thatthe injectable material can be delivered through the opening at adesired dose, for a desired period of time and/or to a desired depth(e.g., cutaneous, subcutaneous, intramuscular, etc.) (FIG. 31). Inembodiments, the charge can generate relatively large amounts of gas butrelatively low amounts of heat. Preferably, the pressure generated bythe charge does not enlarge the opening that can cause discomfort,and/or allow the opening to decrease in size, which can decrease theeffectiveness of the injection by allowing the injectable material toleak back out of the opening. As an example, in some embodiments, thecharge is capable of generating a relatively low initial and finalpressures, such as about 700-800 psi and 200-300 psi, respectively.However, the latency of the pressure profile of the charge can berelatively large, such as about 500 msec.

[0175] By combining or loading the trigger, the propellant, and/or thepassive decay material in a controlled manner in a charge cup or cavity,the charge can generate a pressure profile that is a combination of thepressure profiles of the trigger, the propellant, and/or the passivedecay material, and which can effectively deliver the injectablematerial (FIG. 32).

[0176]FIG. 33 shows an example of a charge having three componentsloaded in a charge cup or cavity 300. Starting at a distal end, thecharge has an igniter 302 (e.g., 75 mg of BKNO₃), a passive decaymaterial 304 (e.g., 60 mg of gum arabic), and a propellant 306 (e.g.,120 mg of CuO/5 aminotetrazole). The sequence of the pyrotechnicmaterials can be adjusted according to the pressure profile desired,e.g., igniter/propellant/igniter. Similarly, the quantities of thepyrotechnic materials can be adjusted. At a distal end, charge cup 300has a burst membrane 308 that acts a pressure dam so that apredetermined pressure can build up in the charge cup before themembrane ruptures and pressure is released to propel, e.g., the chargesleeve and piston. In other embodiments, the membrane can be replacedwith, for example, a shear pin.

[0177] In operation, a user can trigger the charge by passing a currentthrough a filaments, which can extend through the igniter. Triggeringthe charge causes the igniter to burn first, followed by the decaymaterial, and then the propellant. Thus, the charge is capable ofproviding a multi-stage reaction that can deliver the injectablematerial with a desired pressure profile.

[0178] The desired pressure profile can also be controlled by tuning orshaping the charge and/or the pyrotechnic materials. For example, thecharge can be shaped by changing the shape of the charge cup or cavity.The charge cup or cavity can have a narrow distal end relative to thedistal end; a diverging or converging longitudinal cross section; and/ora narrowed throat region along the longitudinal axis. The charge can besolid, e.g., like a cigarette, or hollow, e.g., by using a fillermaterial. The pyrotechnic materials can be formed in different shapes,such as spheres, rods, plates, etc., to change the surface area tovolume ratio, thereby affecting the burn rate and providing differentburning characteristics. The pyrotechnic materials can be granular orpelletized.

[0179] Numerous charges can be used.

[0180] For example, the charge can be a combination of solid materialsfor two or more stages that includes BKNO₃ and CuO/5 aminotetrazole;thermite-aluminum powder and FeO₂; sulfur/chlorate mixtures; aluminumpowders and potassium chlorate or potassium perchlorate; urazole andKClO₄; or urazole and KNO₃.

[0181] Other examples of charges include a system having solid andliquid materials. Examples include vinegar and sodium bicarbonate;NaMnO₄ (permanganate) and hydrogen peroxide; Na metal and water; Limetal and water; and quick lime and water. This system can also be usedas a percussive detonator in which the NaMnO₄ is used to catalyze therapid breakdown of hydrogen peroxide if greater than 70%. Establishingfirst and second stages for a charge could be implemented by physicalsegmentation of two reaction chambers, or in having a more soluble outerzone of solid reactant, and an inner zone of less soluble phase to slowthe reaction. This can be accomplished by compounding and pelletizing.

[0182] Other examples of charges include a system having liquid-liquidmaterials. While sometimes referred to as hypergolic, or hypergol fuels,these systems could be packaged in separate containers. When thecontainers are physically breached, they react quickly. Examples includemonomethyl hydrazine and nitrogen tetra oxide, Aerozine-50, andCompetitive Impulse, Non-Carcinogenic Hypergol or CINCH, which can be anall-purpose replacement for a wide variety of hydrazine andhydrazine-based fuels.

[0183] In some embodiments, physical contact is used as the principalignition mechanism. An igniter is pressed into direct contact with asecondary reactive material such as a propellant. When this type ofconfiguration is employed, it is sometimes referred to as a “first-firecomposition”. In some cases, the “first-fire” includes a mixture, suchas 50/50, of the ignition mix and the material that it is intended toignite.

[0184] Examples of granular or pelletized igniter compositions are:BKNO₃ (Boron/Potassium Nitrate); ALCLO (Aluminum/Potassium Perchlorate);MAG-TEF (Magnesium/Teflon); MTV (Magnesium/Teflon/Viton); BP (BlackPowder). Examples of igniter compositions utilized in “first-fire” mixesare: A1A (Iron Oxide/Diatomaceous Earth/Zirconium; ZPPV(Zirconium/Potassium Perchlorate/Viton); TiCuO (Titanium/Copper Oxide);BBC (Boron/Barium Chromate); BCC (Boron/Calcium Chromate); BBCTiPP(Boron/Barium Chromate/Titanium/Potassium Perchlorate).

[0185] While the use of a charge in connection with certain injectionsystems has been described above, the invention is not so limited. Ingeneral, the charges described herein can be used in any injectionsystem (e.g., any needleless injector) properly configured to house suchcharges (e.g., having an appropriate charge cup or cavity).

[0186] Various combinations of charge materials can be used.

[0187] The following examples are illustrative and not intended to belimiting.

EXAMPLES

[0188] In some embodiments, a charge includes a propellant material,here, 5-AT, and a trigger material, here, a mixture of KClO₃ andsucrose. The charge is placed in a closed finite volume, such as acharge cavity. The propellant material (5-AT) is placed on the bottom ofthe charge cavity, and the trigger material is placed on the propellantmaterial. The propellant and/or trigger material can be compacted, e.g.,about 50-250 psi, or minimally packed. The trigger material can beactivated, for example, by passing a current through a wire filament orusing concentrated sulfuric acid. One or more other materials, such as apassive decay material (e.g., gum arabic) or a heat generating material(e.g., B/KNO₃) can be placed between the propellant and the triggermaterials, depending on the desired pressure profile.

[0189]FIG. 39 shows a pressure profile (pressure as a function of time)capable of providing a needleless injection, e.g., with minimizeddiscomfort. The pressure profile was produced by a charge of 50 mg of 5AT, compacted under 200 psi, and 33 mg of a mixture of KClO₃ and sucrose(22 mg KClO₃ and 11 mg of sucrose) over the 5AT. The charge cavity had adiameter of about {fraction (3/16)} inch. The depth, i.e., the distancebetween the open distal end of the charge cavity and distal end of thecharge, was about 0.191 inch.

[0190] The pressure profile generally increases rapidly, e.g., overabout 2-3 msec, to a peak pressure 511. The pressure then decreases to atail pressure 513. The peak pressure can decrease to the tail pressurerelatively flatly to produce a plateau region 515 with a plateaupressure. In some embodiments, the peak pressure can decrease relativelysharply, e.g., approximately exponential. It is believed that the peakpressure creates an opening, e.g., in the subject, through whichinjectable material can be delivered, and the plateau pressure maintainsthe opening so that injectable material can be continued to bedelivered, e.g., without the opening closing and injectable materialleaking back.

[0191] Without wishing to be bound by theory, it is believed that thepressure profile is a function of one or more parameters or variables.By adjusting these parameters or variables, the pressure profile can beadjusted to provide a desired pressure profile. For example, thepressure profile can be adjusted to inject subjects with differenttissue structure, to inject different types of tissue on a subject, orto inject different types of injectable materials. Some of thesevariables include the amounts of components, e.g., the trigger or thepropellant material, that form the charge; the compositions of thecomponents of the charge; the degree of compaction of the components inthe charge cavity, e.g., the apparent density of the components; thedepth; and the void volume of the charge cavity. The void volume isapproximately equal to the difference between the volume of the chargecavity and the total volume of the components of the charge. In someembodiments, the void volume is the empty volume between the triggermaterial and the distal end of the charge cavity, e.g., where the burstmembrane is positioned.

[0192] Generally, the amount of trigger material is proportional to thepeak pressure and the tail pressure. For example, increasing the amountof trigger material can increase the peak pressure and the tailpressure. Similarly, the amount of propellant material is related to theplateau pressure and the tail pressure. For example, increasing theamount of propellant material, such as 5 AT, increases the plateaupressure and the tail pressure.

[0193] The degree of compaction affects the shapes of the pressureprofile curve. High compaction can produce a plateau-shaped curve. Lowor minimal compaction can produce a curve that is not plateau-shaped,e.g., one that decreases in an exponential-like manner.

[0194]FIG. 40 shows a pressure profile for a charge having 50 mg of 5-AT(compacted by hand packing) and 39 mg of a trigger mixture (26 mg ofKClO₃ and 13 mg of sucrose). The depth was 0.190 inch. Compared to FIG.39, hand packing, i.e., lower compaction, of the propellant, andincreasing the amount of trigger provides a relatively higher peakpressure (about 6125 psi to about 5000 psi).

[0195]FIG. 41 shows a pressure profile for a charge having 50 mg of 5-AT(compacted under 210 psi) and 39 mg of a trigger mixture (26 mg of KClO₃and 13 mg of sucrose). The depth was 0.190 inch. Compared to FIG. 40,the degree of compaction is higher. As a result, the peak pressure islowered (about 6125 psi to about 4812 psi), but the tail pressure isincreased (about 2500 psi to about 3500 psi).

[0196]FIG. 42 shows a pressure profile for a charge having 50 mg of 5-AT(compacted under 220 psi) and 39 mg of a trigger mixture (26 mg of KClO₃and 13 mg of sucrose). The depth was 0.190 inch. Compared to FIG. 41,the degree of compaction is higher, which increases injection time,i.e., the time it takes for the pressure profile to decrease from thepeak pressure to the tail pressure.

[0197]FIG. 43 shows a pressure profile for a charge having 50 mg of 5-AT(compacted under 220 psi) and 31.5 mg of a trigger mixture (21 mg ofKClO₃ and 10.5 mg of sucrose). The depth was 0.250 inch. Compared toFIG. 42, lowering the amount of trigger material and increasing thedepth, lowers the peak pressure (from about 5125 psi to about 3875 psi)and increases the injection time.

[0198]FIG. 44 shows a pressure profile for a charge having 50 mg of 5-AT(compacted under 50 psi) and 36 mg of a trigger mixture (24 mg of KClO₃and 12 mg of sucrose). The depth was 0.190 inch. Compared to FIG. 39,increasing the amount of trigger material and decreasing the degree ofcompaction, increases the peak pressure (from about 5000 psi to about5687 psi) and tail pressure (from about 2250 psi to about 2500 psi),slightly increases the injection time.

[0199]FIG. 45 shows a pressure profile for a charge having 50 mg of 5-AT(compacted under 100 psi) and 36 mg of a trigger mixture (24 mg of KClO₃and 12 mg of sucrose). The depth was 0.190 inch. Compared to FIG. 44,increasing the degree of compaction decreases the peak pressure (fromabout 5687 psi to about 4312 psi) and increases the injection time.

[0200]FIG. 46 shows a pressure profile for a charge having only 31.5 mgof a trigger mixture (21 mg of KClO₃ and 10.5 mg of sucrose). The depthwas 0.070 inch. Compared to FIG. 39, removing the propellant results ina rapid decrease from the peak pressure.

[0201] In some embodiments, the charge can further include B/KNO₃, anexample of a material capable of generating high heat and low gas,between the propellant and trigger materials. The B/KNO₃ is capable offurther expanding gases generated by the trigger material and increasingthe combustion kinetics of the propellant. Generally, the B/KNO3 canincrease the peak pressure, the plateau pressure, and/or the tailpressure.

[0202]FIG. 47 shows a pressure profile for a charge having 50 mg of 5-AT(compacted under 210 psi) and 39 mg of a trigger mixture (26 mg of KClO₃and 13 mg of sucrose). The depth was 0.220 inch. 20 mg of B/KNO₃(compacted under 40 psi) was placed between the 5-AT and the triggermixture. The B/KNO₃ generally provided a relatively high peak pressure(about 5562 psi), a relatively high plateau pressure (about 4875 psi), arelatively high tail pressure (about 3812 psi), and a relatively shortinjection time.

[0203]FIG. 48 shows a pressure profile for a charge having 50 mg of 5-AT(compacted under 220 psi) and 21 mg of a trigger mixture (14 mg of KClO₃and 7 mg of sucrose). The depth was 0.190 inch. 20 mg of B/KNO₃(compacted under 40 psi) was placed between the 5-AT and the triggermixture. Compared to FIG. 47, a decrease in depth and the amount oftrigger material lower the peak pressure (from about 5562 psi to about3812 psi) but slightly increase the slope of the plateau region.

[0204]FIG. 49 shows a pressure profile for a charge having 30 mg of 5-AT(compacted under 210 psi) and 36 mg of a trigger mixture (24 mg of KClO₃and 12 mg of sucrose). The depth was 0.130 inch. 10 mg of B/KNO₃(compacted under 40 psi) was placed between the 5-AT and the triggermixture. The pressure profile has a double peak with a relativelyrapidly decreasing tail.

[0205] For a given charge, the pressure profile can be modified bymodifying the depth. Modifying the depth can produce pressure profileshaving both an approximately exponentially decaying region and arelatively flat plateau region.

[0206] FIGS. 49 to 54 show pressure profiles for a charge having 30 mgof 5-AT (compacted under 210 psi), 10 mg of B/KNO₃ (compacted under 40psi), 36 mg of a trigger material mixture (24 mg of KClO₃ and 12 mg ofsucrose). In FIG. 49 the depth was 0.130 inch; in FIG. 50, the depth was0.135 inch; in FIG. 51 the depth was 0.145 inch; in FIG. 52, the depthwas 0.155 inch; in FIG. 53, the depth was 0.165 inch; and in FIG. 54,the depth was 0.175 inch. Controlling the depth can change the shape ofthe pressure profile, e.g., whether the profile has a rapidly changingportion and/or a relatively flat portion.

[0207] A pressure profile can be modified, e.g., tailored, in whole orin part, by modifying one or more of the variables described above.

[0208] Other embodiments are within the claims.

What is claimed is:
 1. An injection system, comprising: an injectordefining a first cavity in fluid communication with an orificeconfigured for needleless injection; and a housing inside the injectorand defining a second cavity, the housing different than the injector,wherein the injection system is configured to transfer a fluid from thesecond cavity to the first cavity.
 2. The system of claim 1, wherein theinjector is formed of a first material, and the housing is formed of asecond material different than the first material.
 3. The system ofclaim 2, wherein the first material comprises a polymer.
 4. The systemof claim 2, wherein the second material comprises a glass.
 5. The systemof claim 1, further comprising a first movable member between the firstcavity and the second cavity.
 6. The system of claim 5, wherein thefirst movable member defines a lumen.
 7. The system of claim 5, furthercomprising a second movable member between the first movable member andthe second cavity.
 8. The system of claim 7, wherein the first movablemember is configured to engage with the second movable member such thatthe first cavity is in fluid communication with the second cavity. 9.The system of claim 5, wherein the first movable member is configured tobe substantially stationary until the first movable member is moved by apropellant of the injection system.
 10. The system of claim 5, whereinthe first movable member comprises a tab configured to separate from thefirst movable member at a predetermined force.
 11. The system of claim10, wherein the tab is engaged with the injector.
 12. The system ofclaim 1, wherein the injector and the housing are substantially coaxial.13. The system of claim 1, wherein the second cavity is defined by thehousing and two movable members.
 14. The system of claim 1, furthercomprising an injector cap connectable to the injector, the injector capconfigured to move distally to transfer the fluid from the second cavityto the first cavity.
 15. The system of claim 14, wherein the injectorcap is connectable to the injector by a threaded connection.
 16. Thesystem of claim 1, further comprising a charge cup in the injector. 17.The system of claim 16, further comprising a charge in the charge cup.18. The system of claim 17, wherein the charge comprises at least twodiscrete materials.
 19. The system of claim 18, wherein the at least twodiscrete materials have different combustion characteristics.
 20. Thesystem of claim 1, wherein the second cavity is defined by the housingand a movable member.
 21. The system of claim 20, wherein the movablemember is formed of two different materials
 22. The system of claim 20,wherein the movable member comprises a rubber.
 23. A method, comprising:providing an injection system, comprising: an injector defining a firstcavity in fluid communication with an orifice configured for needlelessinjection; and a housing inside the injector and defining a secondcavity, the housing different than the injector; and reducing the volumeof the second cavity to transfer a fluid from the second cavity to thefirst cavity.
 24. The method of claim 23, further comprising flowing thefluid through a movable member between the first and second cavities.25. The method of claim 23, further comprising piercing a member betweenthe first and second cavities.
 26. The method of claim 23, wherein theinjection system further comprises an injector cap connectable to theinjector, and reducing the volume comprises moving the injector captoward the orifice.
 27. The method of claim 26, wherein moving theinjector cap comprises twisting the injector cap.
 28. The method ofclaim 23, further comprising moving the fluid through the orificecharge.
 29. The method of claim 28, wherein the charge comprises atleast two discrete materials.
 30. The method of claim 29, wherein the atleast two discrete materials have different combustion characteristics.